Dr. Neville Wilson, 20 August, 2014.
Public health messages, throughout the Western world, are vocal about the dangers of excess salt in the diet, warning of increased risks for high blood pressure, cardiovascular disease, heart failure and premature death.
The United States Department of Agriculture (USDA) declares that salt is a greater threat to health than fats, sugar and alcohol, a warning that is echoed by National Health bodies in Ireland and the UK.
Are these conventional warnings supported by good science and clinical evidence, and are they thus valid as dietary recommendations for a population that is concerned about it’s health and wellness ?
A large body of evidence is on record, reporting outcomes from clinical studies, which continues to ask the question, “is salt harmful to health, or is salt an essential component of a healthy diet, and not to be feared by consumers ?”
A recently reported clinical study made headline news by challenging the conventional view, and also the current dietary guidelines, that salt intake posed a threat to health.
The conclusions reached by the study authors was that low salt intake, rather than a high intake, posed the greater risk to human health.
SALT STUDIES FROM A RECENT NEW ENGLAND OF MEDICINE JOURNAL (NEJM) – 14 August 2014.
Three important clinical papers were published in a recent edition of the New England Journal of Medicine, challenging the conventional view that high levels of salt intake are a risk for high blood pressure and premature heart disease.
These papers deal with the important questions of (i) Sodium (salt), Potassium & Blood Pressure, (ii) Urinary Sodium and Potassium Excretion, Mortality and Cardiovascular Events, and (iii) Sodium (salt) Consumption and Cardiovascular Mortality. (1)
These important questions have received considerable attention from various researchers over a lengthy period of time, and several studies have been published, in the past, prompted by questions regarding the purported health dangers of salt ingestion.
The recent NEJM papers report the dietary salt intake and urinary excretion of sodium in 100, 000 persons in 17 countries, measured over a 24 hour period, and correlated with their risk for high blood pressure and premature death.
(Urinary output of sodium is a surrogate measure for sodium chloride, or salt, intake in the diet).
In this new study those whose sodium intake was LESS than 3 grams/day had a 27% higher risk of death and heart disease, than those who had consumed an excess of 3 grams of sodium per day.
The American Heart Association (AHA) and the World Health Organization (WHO) recommend a safe dietary daily intake of 1.5 grams to 2 grams of sodium per day, and these recommendations are reflected in the health policies of many Western countries, including Ireland and the UK.
The NEJM paper suggests that we may be consuming too little salt for a healthy cardiovascular system !
The National Institutes of Health (NIH) introduced the National High Blood Pressure Education Programme to the American population in 1972 to help prevent hypertension, even though at that time there was no credible science to back up their health warnings !
Jeremiah Stamler, a leading American Cardiologist at the time, acknowledged that the data for incriminating salt as a cause for hypertension was “inconclusive and contradictory”, and later repeated his conviction that studies in this regard were “inconsistent”.
In this recently published NEJM article the findings challenge the purported benefit of aggressively reducing sodium (salt) intake, and raise critical questions about the scientific validity of the current guidelines.
In the current war on obesity and heart disease salt has been vilified as public enemy number one, and the “eat less salt” has been an integral part of public health messages and dietary warnings by health professionals.
Are we to place our confidence in these public dietary warnings, and will public adherence to such directives translate into healthy outcomes and a reduction in chronic disease and premature death ?
Or are these recommendations without a scientific basis and misguided policies ?
Is there a greater body of evidence that can answer these critical questions ?
The present study results do have the limitation of being a single urinary measurement, whereas previous studies have been 24 hour urinary collections for the measurement of excreted sodium.
IS THERE MORE EXTENSIVE EVIDENCE ?
The long term safety, or harms, of salt have never been adequately tested in long term studies, despite the strong official recommendations from several sources, that dietary salt restriction is essential to good health.
Nutritional Guidelines published in 1983 by The National Advisory Committee on Nutrition Education (NACNE) in the UK, included recommendations to reduce dietary salt intake, and evoked strong critical objections from several leading scientists on the grounds that substantial evidence for the recommendations was not forthcoming.
The objections included strong statements about the “positive value” of salt in the diet, which was “totally ignored” in the NACNE recommendations. (2)
Several studies over many years have investigated the relationship between salt intake, hypertension, and heart disease.
Some of these studies have shown a positive association (3) (4) (5), while others have shown a negative association (6) (7) (8)
THE INTERSALT STUDIES 1988.
Early population based studies examined the associations between high dietary salt intake and blood pressure.
INTERSALT was an international study involving 52 centres in 32 countries, in which electrolyte excretion and blood pressure (BP) were measured in 10,079 men and women, to establish a possible correlation. No consistent association between salt intake and blood pressure was found throughout these several studies. (9)
INTERSALT REVISITED 1996.
The first INTERSALT Report was revisited in 1996 in an attempt to resolve the long-standing controversy about the purported ill effects of increased sodium intake.
The authors reported a strong positive association of urinary sodium with increased blood pressure and “recommended a decrease in dietary salt intake in populations for the purpose of preventing and controlling adverse blood pressure”. (10)
META-ANALYSIS 1996:
In a meta-analysis of 56 random-controlled trials (RCT) reported in the Journal of the Medical Association (JAMA), findings suggested that dietary sodium restriction for older hypertensive individuals might be beneficial, but the evidence in the normotensive population (with normal blood pressures) did not support the current recommendations for universal dietary salt restriction. (11)
SCOTTISH HEART HEALTH STUDY 1997.
This study, reported in the British Medical Journal 1997, showed that a 24 hour intake of sodium predicted coronary heart disease in women, but not in men. The weakness of this study is that a single 24 hour collection was conducted, which may not significantly characterise an individual’s habitual salt intake. (6)
NHANES STUDY I (1971-1975)
( First National Health and Nutrition Examination Survey)
Baseline medical and nutritional information was extracted from a sample of 11,348 American males and recorded between 1971 and 1975, with details of any deaths documented in 1992.
Correlations between salt intake and deaths recorded revealed that fewer deaths, from cardiovascular, or any other cause, were associated with higher intakes of salt. (12)
An analysis of this survey by Dr.Helen Whalley showed that “the heart attack fatality rate among those on a low sodium diet was 20% higher than those on normal diets”. (13)
NHANES STUDY II (1992 – 2005)
Researchers at Albert Einstein College of Medicine analysed data obtained from 7,278 men and women who had participated in the 2nd National Health and Nutrition Examination Survey, and found that lower salt intakes were associated with an increased risk of dying from cardiovascular disease.
Assistant Professor of Epidemiology and Population Health, Prof. Hillel Cohen, reported to an American Heart Association meeting in 2005 “significant associations between lower salt and cardiovascular mortality, and no subgroup, that actually benefited from a lower sodium diet”.
He showed from the data, that a daily intake of less than 6 grams of salt (1 teaspoon) was associated with a 50% higher risk of heart disease, concluding that the “data do not support the current recommendations” to restrict dietary salt intake. (14)
This study was a significant challenge to the prevailing notion that salt intake in excess of 2,4 grams of sodium per day, equivalent to 6 grams or 1 teaspoon of salt per day, posed a risk for death from heart disease. (1 gram sodium = 2.5 grams salt)
Dr. Cohen cautioned the promoters of the National Guidelines and urged them to “go back and study the data”.
A META-ANALYSIS (1998) reported in the Journal of the American Medical Association (JAMA) evaluated the outcomes of 58 clinical trials published between 1966 and 1997, seeking to resolve the prevailing controversy about the health hazards of salt intake.
This review of the clinical evidence found that salt restriction did result in slight blood pressure reductions, but also elevations of LDL, prompting the authors to conclude that “these results do not support a general recommendation to reduce sodium intake”. (15)
The Rotterdam Study (2005).
A European study involving nearly 8000 middle aged people looked at the effects of salt intake on blood pressure, stroke and any form of heart disease.
The study showed no significant effects on blood pressure from a salt intake of up to 16 grams per day, and stroke risk only at intakes in excess of 21 grams per day.
There was no adverse effect on the cardiovascular system, even at these levels, according to the reported data, discounting the national health warnings to reduce salt intake to less than 6 grams ( 1 teaspoon) per day. (16)
NHANES STUDY III (1988 – 1994) Reported in 2008.
The 3rd National Health and Nutrition Examination Survey (NHANES III) tested the popular hypothesis that sodium restriction (as in sodium chloride, which is table salt) might effectively lower blood pressure (BP) and reduce cardio-vascular disease (CVD), and deaths from all causes, in an adult population of 8699 adults aged over 30 years, recruited between 1988 and 1994.
The conclusion of this study was that a lower intake of salt was associated with a higher risk for death. The association was modest, and not statistically significant, but did suggest that for the general American adult population higher salt intake was unlikely to be associated with a higher rate of CVD or all cause mortality. (17)
STUDIES IN 2010 :
Three Salt Reports in 2010 did conclude that modest reductions in dietary salt intake (3 grams per day) could reduce the risk for cardiovascular disease, and also medical costs for treating heart disease victims. (18) (19) (20).
The authors discounted the criticism that “reverse causality” might explain the results, by stating that all participants were healthy before the study, and that all cases of pre-existing cardiovascular disease had been excluded.
In other words, any adverse outcomes observed were not the cause of the low salt levels measured, but the consequence of low salt intake.
However, these commentaries ignored the inconsistency of the association between blood pressure and salt intake in previous observational studies.
2 STUDIES IN 2011 :
Ist Study – JAMA 2011 VOL 305, NO.17:
2nd Study- JAMA 2011 VOL 305, NO.20 :
Two salt studies reported in the Journal of the American Medical Association (JAMA 2011) examined “Fatal & Nonfatal Outcomes, Incidence of Hypertension, and Blood Pressure changes in Relation to Urinary Sodium Excretion” between 1985 and 1990. (21).
1ST SALT STUDY 2011: (JAMA 4 May 2011)
In a prospective population study involving 3681 participants, without cardiovascular disease, and followed for 7.9 years, high sodium excretion by the kidneys correlated with a decrease in the number of deaths.
In the low sodium excretion group there were 50 deaths, compared to 24 deaths in the medium sodium excretion group, and 10 deaths in the high sodium excretion group.
After 6.5 years of the study there was no increase in the risk for hypertension in the high sodium excretion group. In this high sodium group the risk was lower than in the low or medium sodium excretion groups.
In this population based cohort, systolic blood pressure, but not diastolic blood pressure changes, over time, aligned with a change in sodium excretion, but the association did not translate into a higher risk of hypertension or cardiovascular complications.
In the light of these findings the authors concluded that “the earlier population based observational studies ignored the inconsistency of the association between blood pressure and salt intake”.
They concluded that “the assumption that lower salt intake would in the long run lower BP, to our knowledge, has not yet been confirmed in longitudinal population based studies”. (21)
SECOND SALT STUDY 2011: (JAMA Nov 23/30, 2011)
In this study researchers at McMaster University, Florida, evaluated urinary excretion of sodium and potassium (surrogates for salt intake) and it’s associations with cardiovascular events in patients with established cardiovascular disease or diabetes mellitus. (22)
Two cohorts from the ONTARGET and TRANSCEND trials (2001-2008) were included in the 101,945 patients from 17 countries.
With a baseline of 4 – 5.99 grams of sodium per day, urinary excretions of sodium in excess of 7 grams were found to be associated with an increased risk for all cardiovascular events, and a sodium excretion of less than 3 grams per day was associated with an increased risk for cardiovascular mortality, hospitalization and congestive heart failure.
They concluded that a sodium intake of between 3-6 grams per day was associated with a lower risk of death and cardiovascular events than either a lower or higher salt intake.
This was explained as a J shaped association between sodium excretion and cardiovascular events.
Although the methodology and findings from this study have received criticism from some quarters, there has been general agreement about the uncertainty regarding the optimal daily intake of sodium, which confers most protection against the risk of cardiovascular disease. (23)
The World Health Organisation (WHO) recommends a sodium intake of less than 2 grams per day, based on small and short term studies in primary prevention populations. (24)
A COCHRANE COLLABORATION REVIEW (2012) :
In this review the Cochrane Collaborators came to the same conclusion that low salt intake was detrimental to health, and added that by decreasing salt intake, consumers were increasing the levels of other harmful risk factors for premature death.
CONCLUSIONS :
Findings from prospective cohort studies evaluating the association between sodium intake and cardiovascular events, have been conflicting, with some studies showing a positive association, others a negative association.
This new NEJM study brings the longstanding controversy to the fore, with support from earlier findings that low intake of dietary salt may increase the risk for death from heart disease.
These reports support the view that dietary salt is an important component of a healthy diet, and that a decreased intake of salt may present a real threat to human health, by triggering hormonal changes (Renin and Angiotensin) that regulate blood pressure and cardiovascular health.
WHAT ARE WE TO MAKE OF THESE FINDINGS AGAINST THE BACKGROUND OF CONVENTIONAL WARNINGS THAT SALT INTAKE SHOULD BE RESTRICTED AS A HEALTH PREVENTATIVE MEASURE ?
We have repeatedly been warned about the health hazards of eating too much salt, with official dietary guidelines issuing repetitive directives to cut down on salt intake, and to make dietary choices that are “low in salt”
These directives are not dissimilar from those which constantly issue health warnings about eating too much fat, on the assumed grounds that diets high in fat will contribute to obesity and heart disease, with increased risk for premature death.
We are thus urged by conventional health providers to also cut down on fat intake, and to “eat less fat”
THE WAR ON OBESITY:
In the current war being waged on obesity, SALT has been incriminated by policy makers, as a dietary item that needs to be restricted, and added to the list of FATS and SUGAR that need to be branded as dietary culprits.
Current perceptions about the harmful effects of excess salt intake are embodied in official policy statements issued by the Irish National Dietetic Institute (INDI) and the Irish Heart Foundation (IHF) whose recommendations are to restrict salt intake to 3 grams per day (1/2 teaspoon) for adults with a maximum of 6 grams per day, and less than 4 grams per day for children. (25)
They also reflect the dietary policy statements of the United States Department of Agriculture (USDA), the American Heart Association (AHA), and the National Institutes of Health in the USA. (NIH).
More recently, the dangers of excess sugar has been added to these dietary warnings, prompting some dieticians to formulate the slogan HFSS to represent the 3 major culprits to be avoided in the pursuit of good health.
Thus, HIGH FATS, SALT & SUGAR (HFSS) have become the declared villains, each and all to be avoided, or restricted, in daily consumption, as the nation wages war on obesity, diabetes, heart disease, and premature death.
These official declarations of foods that are harmful to health, and to be limited in daily intake, have been seized upon by several sectors of the food industry who proudly advertise their labeled products as being “fat free”, “low in fat”, or “low in salt”.
ARE THESE HEALTH WARNINGS VALID ?
How valid are these ‘HEALTH WARNINGS”, in terms of scientific support, and can consumers be confident that obedience to these dietary directives will translate into health and longevity ?
WHAT ABOUT SUGAR?
At last, SUGAR too, has been identified as a major culprit in causing obesity, diabetes and heart disease, but dietary policy statements do not go far enough in exposing the categories of popular foods that camouflage high levels of hidden sugars, as found in many types of commonly consumed carbohydrates.
Sugar, in the form of Glucose, is a molecular component of carbohydrates, and very little has been said in policy statements about the dangers of excess carbohydrate in the diet.
Neither has much been said in public health statements about the health dangers of High Fructose Corn Syrup (HFCS), ubiquitous in the modern diet. (26)
Conversely, dietary carbohydrates have been promoted historically as the most important component in dietary selections, as illustrated by the popularity and the promotion of the FOOD PYRAMID for many years, which recommended as much as 55% to 70% of daily intake in the form of carbohydrates. (26 )
We have not witnessed the stern warnings about excess carbohydrate ingestion, as we have had about excess salt, or excess fat ingestion, despite decades of evidence that carbohydrate excess is a major factor in the development of obesity, diabetes and heart disease !
WHAT ABOUT FATS ?
Fats, too, have for many years been vilified by spokespersons in the health industry, as a cause for heart disease, prompting calls for “low fat diets” as a strategy to combat heart disease and premature death.
The public health message that fats are unhealthy and pose a risk for heart disease, has been readily seized upon by the food industry, which proudly labels popular brands as “fat free” or “low in fat”, duping the consumers into the false belief that such foods are “heart healthy”.
Critical evidence will show that such foods are not heart healthy, since they are likely to contain high levels of sugar, (carbohydrates), polyunsaturated fats and trans fats, all known to raise risks for obesity and heart disease. (26)
It is only recently that the same policy regulators who historically vilified fats, have retracted their earlier views, and acknowledged that “not all fats are bad” and have conceded that there are “good fats” as well as “bad fats” (27)
This message now forms part of the official dietary recommendations, but does not go far enough in publicly stating that saturated fats, contrary to conventional teaching, are supportive of good health and do not cause obesity or heart disease, as is stated in current public health policy. (27)
SO, WHAT ABOUT SALT ?
The conventional warnings about SALT restriction, also need to be critically assessed, in the light of clinical reviews over several decades, that question the wisdom of such stern public warnings.
Since conventional wisdom espouses the notion that dietary salt may raise blood pressure and lead to heart disease in unwitting consumers, dietary recommendations are obliged to include informative statements, regarding the role salt has in a healthy diet, and of the differences between commercialized processed salt and natural salt.
While salt has important biological functions and needs to be part of a balanced diet, greater health benefit may be derived from selecting salt that is natural rather than processed.
Processed salt, as in commercially produced table salt, contains 97.5% sodium chloride and additives which are non essential, (and possibly detrimental to health) and lacks the important trace minerals and elements that are present in natural sea salt.
Natural unprocessed sea salt, as in Himalayan sea salt, or Okinawan sea salt, contains about 84% sodium chloride and 16% of essential minerals and elements which are vital to biological systems.
Salt gives taste to food, and has a pleasurable effect on our taste buds.
In recent history it was widely used it as a food preservative, and in ancient cultures it was highly valued and served as a bartering agent in many forms of cross border trade.
Should the salt warnings be heeded, or can they be safely ignored ?
And is there any credible evidence for the harms, or the benefits, of salt intake, and what does the scientific literature have to tell us about the way we handle dietary salt in our daily lives?
THE HEALTH BENEFITS OF SALT:
Salt and sodium are often used synonymously, and many of the clinical trials will refer to sodium chloride measurements, as an indicator of salt levels.
Salt comprises 40% sodium and 60% chloride, and both are essential for the efficiency of healthy biological functions.
Sodium also has a vital relationship with potassium in biological systems, and the balance between the two must be maintained for the efficiency of ion exchange across cell membranes.
Too little sodium may result in too high a level of potassium, which may disturb the delicate balance essential to good health.
Too much salt, on the other hand with an inadequate intake of dietary potassium, may gave rise to a disturbed balance with harmful effects on several biological systems, including the heart, muscles, brain and thyroid.
The Irish Heart Foundation, in line with the American Heart Association, calls for restrictions in salt intake, and recommends 4 grams of salt intake per day for adults, with a maximum of 6 grams (1 teaspoon) or 2.4 grams of sodium, and less than 4 grams per day for children. (25)
I gram of salt = 0.4 grams of sodium.
1 gram of sodium = 2.5 grams salt.
100 mEq salt = 2.9 grams of sodium = 5.8 grams salt/sodium chloride.
6 grams salt = 1 teaspoon.
Since sodium is an essential ion for nerve conduction, muscle contraction and cell signaling, salt restriction may cause harm, and low levels of sodium in the urine may indicate inadequate intake. (28)
Low salt (sodium chloride) intake may cause alterations to brain function, especially in the elderly. Certain drugs for high blood pressure, often prescribed for the elderly, may cause losses of important electrolytes (sodium and potassium) through kidney and urinary excretion, and impair normal brain function in vulnerable people. (29) (30) (31)
The lack of sodium retention by the kidneys is common in the elderly and in pregnant women (32) and may result in hyponatraemia, or low blood levels of salt (33), swelling in the brain, and may be linked to amyloid plaque formation, a common feature in patients with Alzheimer’s disease. (34)
The human body cannot make salt or sodium chloride, and is dependent for a healthy supply of these nutrients from the diet.
Salt restriction elevates certain hormones that have a regulatory role in the sympatho-adrenergic system, such as renin, angiotensin and aldosterone.
Evidence suggests that even modest reductions in salt, over lengthy periods, may induce strokes, heart attacks and heart failure. (33)
Contrary to these findings, the WHO and the AHA recommend a dietary intake of salt of less than 1.5 to 2 grams of salt per day.
The Irish Heart Foundation recommends 3 grams of salt per day with a maximum of 6 grams. (25)
An interesting finding from the 13 studies reported in the 2011 edition of JAMA, (mentioned above) was that the researchers did not observe a significant association between salt intake and blood pressure until sodium excretion exceeded 6.5 grams per day, much higher than the WHO recommendation for salt intake. (21)
An important consideration regarding increases in blood pressure is that systolic blood pressure (SBP) does increase naturally with age, until the 8th decade of life, and diastolic blood pressure (DBP) increases with age to about 50 and then levels off, or decreases.
These natural age related changes in BP may therefore mask any trends in BP assessment associated with changes observed in 24 hourly urinary sodium collection.
It is therefore difficult to assess the full impact of salt ingestion on health, but there is sufficient evidence to show that salt restriction may produce risks to health, with little benefit.
Problems with SALT consumption :
Global sodium intake was reported to be as high as 4000 mgs (4 grams/day) in 2010, with the estimated salt intake in the USA as high as 3600 mg (3.6 grams / day). These figures exceed the WHO recommendations of less than 2 grams/day.
The sources for such sodium intake includes the vast amounts of processed foods consumed in Western societies, invariably high in harmful chemicals and additives, such as ferocyanide and alumino-silicate and fluoride. (35)
MSG – A SOURCE OF SODIUM:
Sodium may also be found in a vast array of fast foods which may be high in Monosodium glutamate (MSG), a food additive and flavor enhancer, commonly used in Chinese fast food preparations.
MSG contains 78% free glutamate and 21% sodium, and is a common additive in many tinned foods, soups, processed meats and fast food outlets.
Although the FDA has labeled MSG as GRAS ( Recognised As Safe) there is evidence that MSG is an excitotoxin that may trigger the onset of certain brain disorders. (36)
NATURAL SALTS:
Processed salt, such as the commonly used TABLE SALT, is vastly different, and chemically inferior, to natural salt, which contains a healthy balance of vital nutrients.
A variety of natural dietary salts are available from Health outlets, such as Himalayan Crystal Salt, which contains 86 natural minerals, and elements, and is more palatable and safer than common table salt.
Okinawan sea water salt (MASU) is also a natural alternative to table salt, rich in trace minerals and devoid of harmful chemicals.
POTASSIUM INTAKE IS VITAL:
Since processed foods are high in refined salt and low in potassium, it is essential to maintain a healthy balance of sodium and potassium intake in the diet.
It is safe to salt food to taste, using natural salt, providing a diet that contains potassium is included.
The dietary sodium/potassium ratio is vital for healthy biological systems, and potassium depletion may be more harmful that sodium excess, if potassium containing foods are excluded from the diet.
Decreased potassium intake may contribute to fluid retention and increases in blood pressure, irregular heart rhythms and muscle weakness and cramps.
Excessive thirst and constipation may be a sign of potassium depletion, or excess processed salt in the diet.
SOURCES OF POTASSIUM:
Green vegetables are a natural source of potassium, and juicing of greens may supply daily requirements for a balanced intake of electrolytes.
Other foods that are high in potassium are Lima Beans, Squash, Avocado, spinach, broccoli, Brussels sprouts, asparagus and pumpkin.
Fruits containing potassium are papaya, cantaloupe, and bananas.
CONCLUSION AND RECOMMENDATIONS:
⦁ Salt is an essential nutrient and requirement for good health, provided it is natural and not processed.
⦁ Clinical research recommends a cautionary approach to salt restriction, but recommends no more than 6 grams a day.
⦁ Reductions to less than 3 grams per day( ½ teaspoon) may increase the risk of death by 27%, and restrictions to less than the recommended 2.3 grams per day may increase the risk of cardiovascular disease.
⦁ Processed foods are high in sodium and low in potassium, and are detrimental to health, and should be avoided in the interest of good health. More than 70% of dietary salt comes from the “food” in supermarkets and restaurants, while approximately 20% is added at the table, and 10% – 12% comes from natural foods.
⦁ An excess of processed salt intake is likely to occur when the following processed foods are consumed: bread and rolls, processed meats, pizzas, processed poultry, sandwiches, pastas, soups and salty snacks. (2 slices of bread contain 264 milligrams or more than 1/4 gram of processed sodium).
⦁ Potassium intake is vital for balanced nutrient intake, and a variety of green vegetables should be part of a regular daily diet.
Dr. Neville Wilson.
The Leinster Medical Clinic, IRELAND.
20 August 2014.
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Thank you Dr Wilson, for a very interesting article. As a dietitian may I advise INDI is Irish Nutrition and Dietetic Institute for future reference.
Your views are informative and refreshing.
With kind regards,
Isabelle Greene