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What does a healthy keto diet (and nutritional ketosis) tend to do to a patient’s NMR?

Summary In general, research suggests that carbohydrate restriction and nutritional ketosis are associated with larger, presumably less atherogenic LDL particles with fewer small dense LDLs.

It is important to know more about the client’s blood regulation profile including fasting insulin, C-peptide, and fructosamine. Persistent elevations in fasting glucose and hemoglobin A1C are not desirable and should be monitored and address, especially considering her family history of dysglycemia. It’s not clear if she had past issues with blood glucose regulation, dyslipidemia, or weight loss, this information would be important in a comprehensive assessment.

Carbohydrate is a primary fuel source for the body and brain. The RDA for carbohydrate is 130 grams per day based on its role as the primary energy source for the brain. In general, the acceptable macronutrient distribution for carbohydrate is 45-65% of total calories according to the standard dietary reference intakes (USDA. DRI Macronutrients).

However, the brain can shift to ketones for a portion of its energy needs. Nutritional ketosis occurs when carbohydrate intake is low enough to generate beta-hydroxybutyrate at a level between 0.5 and 5.0 mmol/L. Dangerously high ketones are associated with ketoacidosis and metabolic derangement (Noland 2020).

As far as the effect of nutritional ketosis on lipoprotein profiles, some research indicates that therapeutic carbohydrate restriction can help address hypertriglyceridemia, elevated small dense LDL particles, and reduced HDL-C, the most common dyslipidemia associated with type 2 diabetes. Nutritional ketosis has been found to improve these markers as well as hemoglobin A1C in some cases (Athinarayanan 2020).

Systemic review and meta-analysis of 38 randomized trials comprising 1785 subjects suggest that reduction in carbohydrate intake was associated with a shift from small dense LDLs to larger LDLs, a change that could be partly due to weight loss. Smaller LDLs are assumed to be more atherogenic due to their increased susceptibility to glycation and oxidation (Falkenhain 2021).

The effects of two years on a very low carbohydrate diet (less than 30 grams/day) in overweight type 2 diabetics included a decrease in small dense LDL particles and an increase in IDL-2 and large LDL particles that accounted for an observed increase in total LDL-cholesterol. Subjects were categorized as “hypo-“ or “hyper-responders” depending on their LDL levels following intervention.

Also, more individuals in the diet group shifted from atherogenic phenotype B (i.e., high triglycerides and small dense LDLs and low HDL-C) to the more favorable phenotype A compared to the “usual care” group. Neither group had changes in carotid-artery intima thickness or apoproteins. This study used ion mobility to measure lipoprotein subfractions. Therefore, the numerical results are different than NMR but the trends for the lipoprotein subfractionation should be considered comparable (Athinarayanan 2020).

Evaluation of the same subjects at the one-year mark noted that those on the diet decreased mean HbA1C by 1.29% versus an increase of 0.2% in the usual care group. The diet group also experienced significant decreases in hsCRP, LP-IR, and triglyceride/HDL-C ratio, and a significant increase in apoA1. Researchers attributed up to 70% of these improvements to weight loss during the study (Bhanpuri 2018).

Another study using NMR technology compared the effects of low carbohydrate (20% of calories), moderate carbohydrate (40%), and high carbohydrate (60%) intake on lipoprotein subfractionation values after a period of weight loss on a hypocaloric diet. The low carbohydrate group saw the greatest decrease in lipoprotein insulin resistance (LPIR), large triglyceride-rich particles, and Lp(a), and the greatest increase in large HDL-Ps. The LPIR score takes into account triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P) (Ebbeling 2022).

In the case of your client, blood glucose regulation issues may still be present despite her adherence to a low-carbohydrate diet. Micronutrient status should be monitored as well as continued monitoring of blood glucose regulation and lipoprotein biomarkers.

If intake of vegetables and fruits is below the minimum total of 5 servings per day, preferably 7-9 servings per day, it would be prudent to use fruit and vegetable concentrates to provide the phytonutrients unique to these foods.

References

Athinarayanan, Shaminie J et al. “Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes.” Cardiovascular diabetology vol. 19,1 208. 8 Dec. 2020, doi:10.1186/s12933-020-01178-2

Bhanpuri, Nasir H et al. “Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.” Cardiovascular diabetology vol. 17,1 56. 1 May. 2018, doi:10.1186/s12933-018-0698-8

Ebbeling, Cara B et al. “Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia-a randomized controlled feeding trial.” The American journal of clinical nutrition vol. 115,1 (2022): 154-162. doi:10.1093/ajcn/nqab287

Falkenhain, Kaja et al. “Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis.” The American journal of clinical nutrition vol. 114,4 (2021): 1455-1466. doi:10.1093/ajcn/nqab212 https://academic.oup.com/ajcn/article/114/4/1455/6308082?login=true

Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

USDA. DRI Macronutrients. https://www.nal.usda.gov/sites/default/files/fnic_uploads/macronutrients.pdf