Dietary intervention for good health.

On the face of it, it would seem a no-brainer the subject of dietary intervention to promote good health. We all know of the recent epidemic of obesity in our youth, the explosion of diabetes. A lot of it  due to jumbo-sized servings offered by fast food chains. When the rubber meets the road, the ask is made all the more difficult by competing and convincing beer and fast food commercials. If this were not burdensome enough, wading into the matter of diet and health promotion is ever so humbling as there are conflicting data and the situation remains fluid. Accepted dogmas keep being upended. The alternative to promotion of good health is the hoist of the white flag and that cuts against the grain of our oath.

Dietary evaluation sits at the intersection of sacred cultural habits bordering on jingoism, commercial interests purveying information to stroke vanity and monetize on gullibility. Adding fuel to the fire, it enmeshes in the crosshairs of the latest fad accepted with religious fervor. It is not by chance that there is a whole cottage industry promising miracle weight loss with an alphabet soup of names from Atkins to Zone.

This review is meant to ask some pointed questions without any known answers yet  and will point out some unexpected findings. Again the matter is not as simple as we would like to believe. There are a lot of confounding factors and at times it is difficult to isolate one single factor. However, it should be remembered that a food group should never be lionized or demonized.

 

A meticulous approach demands that one looks at population studies to help sort out some of the confusing data (table 1).

Mortality rate from MI by country

Country	Rate/100,000	Rank
Turkmenistan	411	1
Russia	392	8
Guyana	207.86	24
Haiti	161.82	38
Ghana	155.08	44
Trinidad	154.33	45
India	146.11	56
Dominican Republic	129.96	67
Greece	112.40	97
Argentina	106.36	109
Malta	103.64	111
Cuba	100.35	116
USA	86.89	130
Italy	64.95	163
Kenya	44.20	180
France	43.25	181
Japan	40.59	182
South Korea	30.76	183

Table 1 (worldlifeexpectancy.com)

The data are interesting. Russia and its former republics hold the top 10 spots. India has a high rate of mortality even with the highest concentration of people on a vegan diet. Mediterranean ring offers a wide spread of mortality rate from the very low of France to the high of Greece’s, ahead of Cuba’s. The case of India will be addressed later because it is so unexpected. One needs to keep in mind that diet alone doesn’t tell the whole story. Smoking, exercise or lack thereof, genetics and other not yet well-defined factors make a lot of difference.

 

A recent study tried to evaluate if there is such a phenomenon as the perfect diet and looked at several groups of hunter-gatherers that have the lowest rate of cardiovascular disease in the world. In Obesity Reviews, Pontzer et al (5) looked at the Hadza of northern Tanzania, Tsimane of the Amazon and Shuar of Ecuador and found out a very low rate of cardiovascular illness (hypertension, diabetes, stroke, MI). Their diet varies from one another but tends to include a lot fiber, primarily as tubers but it also includes carbs, red meat. Walking is a very important aspect of their daily lives.

 

In their surroundings, they tend to die of infectious illnesses and carry a high infant mortality because of it. Yet when the Tsimane move from their traditional environment to city life and its new dietary regimen, they become highly susceptible to diabetes. In the US, a similar pattern is observed among the Pima Indians of Arizona (3). They have the highest rate of diabetes and diabetic complications in the country whereas their cousins in Mexico who live the traditional life and consume centuries-old diet have no such issue. The lesson to be learned is that traditional diet includes low salt, low glycemic index carbs, low total calories as well as constant physical exercise (one caveat though; this present study shows that Total Energy Expenditure, TEE, is not that much different between hunter-gatherers and city dwellers). Modern city dwellers tend to overeat and also consume a lot of ultra-processed foods and snacks. There is a modern concept called “sensory specific satiety.” It refers to the fact that our exposure to so much food, say at a restaurant, makes it harder to become satisfied even when we are full; we still get the dessert though we don’t need it or don’t still feel hungry.

 

Fats.

 

Cholesterol, saturated fats have had a bad name for quite a long time with scientific evidence either exaggerated or ignored. Basic science teaches us that cholesterol is very important for good health as it makes up our cell wall. This is especially so for our brain where 50% of its dry weight is cholesterol. The original sin took place when the association of atherosclerosis was twinned with cholesterol; from then on cholesterol is primarily seen through jaundiced eyes of a bad molecule. This is not supported by scientific data. The question we need to ask is the following: what’s the pathophysiology of atherosclerosis?

 

The fundamental inciting injury is endothelial dysfunction and this sets up a cascade of events (2). The production of NO is inhibited and this causes an inflammatory process that feeds on itself. Monocytes, T cells combine with defective endothelial cell creating oxidative stress. LDL becomes oxidized, binds to this matrix and then a foam cell is formed (fatty streak). Macrophages secrete additional proinflammatory cytokines-the list of cytokines keeps growing as we learn more- and smooth muscle cells join the fray and start replicating and the process continues. There is plenty of blame to be shared by the system including oxidized LDL, monocytes/macrophages and other cytokines, leading to plaque formation. The plaque can be stable or unstable and subject to rupture and causing thrombosis/occlusion. Concentrating on only LDL misses the point. It is an easy marker to screen and detect but by no means is it the sole or prime suspect. This concept is important to understand because the inflammatory cascade is the fundamental culprit that needs to be stopped to arrest the progress of the process. It comes as no surprise that illnesses associated with inflammation/endothelial dysfunction are known to cause atherosclerosis: diabetes, hypertension, as well as bystanders such as dysfunctional LDL/HDL, low lipoprotein(a), high level of homocysteine. Other predisposing factors are excess alcohol, Chlamydia infection, visceral fat (even in the absence of obesity) and a sedentary lifestyle. What exactly is meant by dysfunctional bystanders? 

• LDL. Total LDL cholesterol doesn’t tell the whole story. It needs to be subtyped. It comes in either pattern A or B. The latter is the small dense type and the one more likely to sink and become oxidized and become involved in plaque formation.
• HDL. It comes in 10 subtypes. The large subtypes are cardioprotective whereas the small dense ones are not. It used to be taught that the higher the HDL, the better. However, a recent study points toward a U-shaped curve where protection diminishes as level of HDL rises above 97 for men and 137 for women (4). This was done in Denmark. It is not yet clear what the implications are but suggestion of dysfunctional HDL, i.e. small dense HDL maybe at play. This adds another layer of puzzle.
• Lipoprotein(a). A high level (>50mg/dl) triples the risk of Acute Coronary Syndrome in patients < 45 years of age and is not much of a factor in patient> 60 yrs. It is not modulated by diet or exercise (1).
• Triglycerides. The exact mechanism is not well known but elevated level seems to be another independent risk factor, especially in women.
• Saturated fats. They are either saturated (SFA), monosaturated (MFA), or polyunsaturated (PUFA). Saturated fats come from animal origin: meat, poultry, dairy, egg as well as coconut, palm or kernel oils. MFA include canola, nut, olive oils. PUFA include safflower, sunflower, sesame, corn soybean oil (8). Trans fats are usually commercially made from PUFA and carry cardiotoxicity. SFAs are further divided into short, medium and long chain. Long chain fatty acids tend to be stored into adipose tissue while medium and short fatty acids are used and not stored. Coconut oil contains 90% of saturated fatty acids and more than 50% of that in the form of form of lauric acid, a medium chain fatty acid. Coconut oil is thought to be cardioprotective, but this issue is not yet settled with some holding the view that as saturated fat it should be cardiotoxic.
• Homocysteine. The association of elevated homocysteine, an amino acid and atherosclerosis is significant for historical reasons because it’s a window into professional bias that can prosper even at the highest academic institutions. A young pathologist, a Harvard graduate, Kilmer McCully, MD, made the discovery in the mid-sixties that in young children with congenital homocystinuria, homocysteinemia caused premature atherosclerosis (15). Furthermore, homocysteinemia can be corrected by taking B vitamins. At the time-even today- the prevailing dogma of lipids as the sole source of atherosclerosis was gaining steam and his own theory that homocysteine was also an independent mechanism of such a process was considered anathema and he eventually lost his position as a faculty member at Mass General and Harvard. Nowadays, it is an accepted factor that can contribute to atherosclerosis and cryptogenic stroke. It competitively binds to atheroma preventing plasminogen to interact and hence enhances thrombosis (13). A diet devoid of vitamin B₁₂ can accelerate the process of atherosclerosis over time despite the enterohepatic recycling of B₁₂, because both B₁₂ and B₆ help in the breakdown of homocysteine into methionine and cysteine respectively.
• Chlamydia. Its exact role is not well elucidated but plaques tend to test positive when compared to control (10). Could it be playing a role more important in countries with high load of infectious diseases?
• Alcohol. The association of alcohol and atherosclerosis is particular and follows a J-shaped curve (14) where small daily consumption (<50gm) and high dose is cardiotoxic. Table 1 offers some tantalizing evidence. In Russia where alcoholism is rampant (along with cigarette smoking), mortality from MI is high while in France where the consumption of moderate amount of red wine is prevalent, the mortality is low. More often than not, consumption of alcohol is tends to be more on the heavy side than the moderate throughout the world. A dose-dependent action of alcohol on oxidized LDL seems to be at play.

All of the cardiotoxic cytokines share the feature of oxidative stress capability. This ability starts a cascade of inflammation that is detrimental to the endothelium and sustains itself in a vicious cycle. Several pathways exist and several noxious agents exist. It is not a one-size-fits-all scenario. Our system is far smarter than that!

 

Carbs.

Carbs have displaced fats as the latest villains. Again, the science doesn’t support this notion. What it does tell us is that there are carbs necessary for healthy living such as fruits and vegetables and there are others that can cause a rapid rise of blood glucose and consumption of such can lead to weight gain and its complications. The fundamental issue is the rapid rise of glucose. This causes release of Insulin and if there’s resistance at the cellular receptor level, then the pancreas keeps producing more of it. Insulin is an anabolic hormone and causes weight gain. As a matter of fact, chronic insulinemia and good health are at opposite ends. There’s now the concept of glycemic index, how quickly a given carb will induce a rise of glucose. The higher the number, the more it needs to be avoided. The following table lists a few carbs with their indices.

 

GRAINS
Quinoa	53
Brown rice, boiled	68
White rice	89
Bulgur	48
Basmati rice	52
DAIRY
Reduced-fat yogurt	33
Ice cream, regular	54
Milk, full fat	41
Milk, skim	39
LEGUMES
Chickpeas	28
Kidney beans	24
Lentils	32
Soya beans	16
VEGETABLES
Potato, boiled	78
Sweet potato, boiled	63
Plantain	55
Carrots, boiled	39
FRUITS
Grapefruit	25
Apple, raw	36
Orange, raw	43
Banana, raw	51
Mango, raw	51
Watermelon, raw	76

Table 2 (health.harvard.edu)

 

Diet.

• Vegan. It falls into 2 groups: lact-ovo-vegans who consume eggs and milk and strict vegans that avoid them. The advantage of this diet is its anti-inflammatory property and as such its cardioprotection. A strict vegan diet has the drawback of vitamin B₁₂ deficiency long term, if it’s not taken separately. This is important.
• Mediterranean. This type relies on a combination of fish, grains, olive oil, fruits, nuts with or without limited use of red wine. This diet is cardioprotective. However, table 1 shows there’s still variable mortality rate. In France where the use of red wine is prevalent has a low rate but other countries such as Greece, Malta have a much higher rate.
• Ketogenic. Although it is a recent craze as a means of weight loss, it has been around for almost 100 years. It was first introduced in 1921 as a therapy of epilepsy in kids. It lost favor when antiseizure medications were found. As an option of losing weight, it gained popularity in spite of initial medical reticence to condone it. The idea of using fats to lose weight certainly upended orthodoxy. In medicine, ketone bodies are usually associated with cellular starvation in DKA and alcohol-induced lactic acidosis. Ketones can be harmful to the neurons. The very idea of using fats to lose fat didn’t sound right. However, people doing it were successful in losing weight. Since then more has been learned about it. Instead of starvation ketosis that is harmful, what is created is nutritional ketosis and it has a diuretic effect and initial weight loss is due to water loss, then it is followed by fat loss because fat stores are reduced (9). Basically, we are fooling the body and forcing it to use fats as the prime source of energy.  Incidentally, myocardium normally uses fatty acids rather than glucose as a prime source of energy-in fact that’s the rationale of using L-carnitine in patients with cardiomyopathy because it catalyzes the breakdown of fats by myocardium and enhances energy utilization by the starving myocyte. Symptoms occur within the first 2 weeks such as diarrhea, vomiting, weakness, muscle cramps, etc. It is called “keto flu.” Beyond 2 years of staying on this diet, there’s no data about its safety. Up till then, a low carb, high fats, low protein diet is found to be safe, albeit with the initial keto flu.
• Low carbs vs. low fat. In obese, type 2 diabetics, both achieve the same weight loss, reduction of A1C after 1 year. Low carbs diet tends to increase HDL slightly, increase in insulin sensitivity. Low carbs diet associated with plant-based fats and protein carry lowest mortality (fat vs. carbs).
• No discussion about modulation method is complete without mentioning the gut. It is now well established that the gut microbiota heavily influences our overall health. Studies done on hunter-gatherers proved that a diet heavy in fiber is associated with an anti-inflammatory population of bacteria in the gut. Since inflammation is the very process we want to stop or arrest, it behooves everyone to consume as much fiber as possible and most certainly population at risk should indulge. See table 3 for examples of high fiber containing food.

Dandelion Greens	Apple
Garlic	Cocoa
Dried figs	Sweet potato (especially with skin on)
Onions	Leeks
Asparagus	Bananas
Oats	Wheat bran
Baked beans	Almonds
Broccoli	Artichoke
Whole-wheat bead	Whole-wheat spaghetti
Pistachio nuts	Carrots
Strawberries	Sweet corn

Table 3

The above will help us decipher some additional population studies. India as stated previously has a large population of people on vegan diet, yet it has a serious epidemic of cardiovascular morbidity. Prabhakaran (7) and Bajaj (6) report the intake of fruits and vegetables is minimal, especially in rural areas and smoking rate is rising. Lack of vitamin B₁₂ in the diet is associated with increased risk of cardiovascular disease via accumulation of homocysteine. Indians even when not obese have visceral fat and this is cardiotoxic. A surrogate marker is obtained by measuring the waist to weight ratio. A vegan diet, despite all its benefits, by itself is not a panacea. We always need to remember that there’s no panacea.

Smoking as a risk factor can’t be overlooked. González-Pacheco (11) in his study points out that cigarette smoking is the most prevalent risk factor in a study done in Mexico City. While the rate of smoking is declining in the US, the opposite trend is noted in other parts of the world, Latin America, Africa and Asia. This represents a major public health dilemma. It’s also an interesting finding in his study that total cholesterol of patients coming with Acute Coronary Syndrome (ACS) was elevated in 24% of cases but dyslipidemia accounted for 85% and low HDL was the most common abnormality. The association of cigarette smoking and dysplidemia is well established (12). Gepner’s data show that cigarette smoking affects HDL primarily. And of course the usual culprits of hypertension and diabetes were also present in González-Pacheco’s study.

 

With all of the above, what can we suggest as nutritional therapy? Any recommendation has to take one’s cultural culinary preference into account. Asking a rice eater to quit using rice is not practical; however, one can suggest a qualitative-basmati over white rice- as well as a quantitative change. There’s no controversy about the combination of fruits and vegetables servings (5/day). There’s no controversy about a high fiber diet, low consumption of alcohol. 1 glass of red wine a day is helpful for the heart, that explains the low death rate of France from MI. Cigarette smoking is a major cardiovascular risk factor. There is an alarming rate of increased consumption of cigarettes in the developing word and latest reports point to the fact noxious substances that wouldn’t be allowed in Switzerland are finding their way into cigarettes produced by that country being exported to the third world countries. Physical activity is a must.

Considering the difficulty to change one’s culinary habits, it would be best to recommend drastic changes to people at highest risk. For example, a diabetic or someone recovering from MI or with known coronary artery disease should be educated about the benefits of a vegan diet. At least it’s an option worth considering.

Fat consumption is a bit controversial. The available evidence is that processed meats such as bacon, sausage, spam, trans fats are cardiotoxic. Avoiding animal fat altogether is not supported by the evidence. The evidence strongly supports the idea of using a diet that relies on a variety of nutrients with a high content of fruits, nuts, vegetables, grains, à la Mediterranean diet is compatible with good health. Palatability is always a factor to be considered. A healthy but not so tasty menu will invariably lead to cheating.

Last but not least, exercise on a regular basis needs to be part of the routine. Sugary drinks that have no nutritional value should be minimized or avoided. Highly processed carbs should also be avoided. High fiber diet is highly recommended.

 

References:

1. High levels of lipoprotein (a) and premature acute coronary syndrome. Rallidis, Loukianos S. et al. Atherosclerosis. 2018;269:29 – 34.
2. Aziz M, Yadav KS. Pathogenesis of Atherosclerosis. Med Clin Rev. 2016, 2:3.
3. Schulz LO, Chaudhari LS. High-Risk Populations: The Pimas of Arizona and Mexico. Curr Obes Rep. 2015;4(1):92-8.
4. Singh K, Rohatgi A. Examining the paradox of high high-density lipoprotein and elevated cardiovascular risk. J Thorac Dis. 2018;10(1):109-112.
5. Pontzer, H., Wood, B. M., and Raichlen, D. A. (2018) Hunter‐gatherers as models in public health. Obesity Reviews, 19: 24–35. https://doi.org/10.1111/obr.12785
6. Bajaj HS, Pereira MA, Anjana RM, et al. Comparison of relative waist circumference between Asian Indian and US adults. J Obes. 2014;2014:461956.
7. Dorairaj Prabhakaran, MD, et al. Cardiovascular Diseases in India Current Epidemiology and Future Directions. Circulation. 2016;133:1605–1620.
8. Boateng L, Ansong R, Owusu WB, Steiner-Asiedu M. Coconut oil and palm oil’s role in nutrition, health and national development: A review. Ghana Med J. 2016;50(3):189-196.
9. Fedorovich SV, Voronina PP, Waseem TV. Ketogenic diet versus ketoacidosis: what determines the influence of ketone bodies on neurons? Neural Regen Res. 2018;13(12):2060-2063.

10. Belland, R. J., Ouellette, S. P., Gieffers, J. and Byrne, G. I. Chlamydia pneumoniae and atherosclerosis. Cellular Microbiology. 2004; 6: 117-127. doi:10.1046/j.1462-5822.2003.00352.x

11. González-Pacheco H, Vargas-Barrón J, Vallejo M, et al. Prevalence of conventional risk factors and lipid profiles in patients with acute coronary syndrome and significant coronary disease. Ther Clin Risk Manag. 2014;10:815-23. Published 2014 Oct 6. doi:10.2147/TCRM.S67945

12. Gepner AD, Piper ME, Johnson HM, Fiore MC, Baker TB, Stein JH. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011;161(1):145-51.

13. Geoffrey H. Tofler, Ralph B. D’Agostino, Paul F. Jacques, Andrew G. Bostom, Peter W. F. Wilson, Izabela Lipinska, Murray A. Mittleman, Jacob Selhub. Association between increased homocysteine levels and impaired fibrinolytic potential: potential mechanism for cardiovascular risk. Thromb Haemost. 2002 Nov; 88(5): 799–804.

14. Kiehl, S, Willeit, J et al. Alcohol Consumption and Atherosclerosis: What is the Relation?

Stroke. 1998;29:900–907

1.https://www.nytimes.com/1997/08/10/…/the-fall-and-rise-of-kilmer-mccully.html

 

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