What happens when health markers and lab results do not improve on a low-carb diet?

On a low-carb, high-fat (LCHF) or keto diet, most health markers and lab results tend to improve.1 However, when that is not the case, this guide will help you troubleshoot unexpected results.
As a reminder, this information is intended for doctors, not for the general public (full disclaimer). Discuss any changes in medication and relevant lifestyle changes with your doctor.

 

1. Triglycerides are rising

Fasting triglycerides (TGs) are expected to go down with LCHF diets because the body is now using TGs as energy, replacing glucose as the body’s main fuel.2 However, TGs are greatly influenced by diet, so they can vary throughout the day.

If triglycerides are rising, first make sure your patient did a water-only fast for 10-14 hours prior to the blood test. Next, check for alcohol consumption and confirm that the patient understands how to follow a low-carb diet (check for “carb creep”). In very rare cases, the rise in TGs may be due to a genetic disorder such as familial hypertriglyceridemia.3

If there is no clear explanation, inquire about coffee consumption. Anecdotally, some clinicians have noticed that coffee consumption is linked to an increase in TGs when a patient is on a low-carb diet.4 While it is not known if this is a clinical concern, eliminating coffee intake may normalize TGs.

What to do: After the above checks and interventions, retest TGs in three months (sooner if TGs are >500 mg/dl). Follow appropriate guidelines if they remain severely elevated.


2. Total cholesterol/LDL is rising

A low-carb, high-fat diet usually improves cholesterol profiles.5

Typically high-density lipoprotein (HDL) cholesterol increases, while triglycerides decrease and low-density lipoprotein (LDL) particles become larger and less dense.6 All three of these changes statistically reduce the risk of future heart disease.7

Generally speaking, LDL remains unchanged or the elevation of total and LDL cholesterol is so small that it is likely clinically insignificant.8 The first step, therefore, is to determine if an elevation in total cholesterol is due to an elevated LDL or other apo B containing lipoproteins, or if it is due to a potentially beneficial elevation in HDL. This is simply done by comparing the pre- and post-diet HDL and non-HDL values.9

The next step is to assess the timeframe One trial showed that a small transient rise in LDL normalized at the 1-year mark.10 Therefore, if there is an early, small increase in cholesterol, it is reasonable to simply monitor this over the next 6-12 months.

However, in some cases, estimated between 5 and 25% of those on a low-carb or keto diet, LDL cholesterol may demonstrate a dramatic, sustained elevation. This seems, from clinical experience, to occur most commonly in lean individuals but can occur in anyone.11

In these situations, we recommend putting LDL increases in context with other risk factors before deciding if medications or dietary changes are warranted. Also note that LDL by itself may not predict cardiovascular risk as well as lipid ratios, such as TC:HDL and TG:HDL ratios, especially in the absence of diabetes or metabolic syndrome.12

In addition to considering other risk factors, such as hsCRP, Lp(a), Blood pressure, smoking status, family history of premature CVD, presence of diabetes or metabolic syndrome, visceral adiposity, and even elevated insulin levels, we recommend performing a comprehensive cardiovascular risk assessment rather than reacting to a single lab value change.

For those with a severe elevation of total cholesterol over 300 mg/dL (7.7 mmol/L) or LDL cholesterol over 200 mg/dL (5.1 mmol/L), we do not have conclusive evidence that these levels are safe, even for those on a low-carb diet with otherwise normal biomarkers (e.g.HDL, triglycerides, insulin, glucose, Lp(a)).

The guidelines are clear that pharmacologic treatment is warranted in such cases. Until we have convincing evidence that this is not a concerning scenario, we suggest consulting the guidelines and having a thorough discussion of potential risks and benefits with your patients.

In the course of your discussion with patients, carefully assess the benefits that they have seen on a low-carb diet to determine if it is worth continuing (it often is).

Read more about cholesterol on a low-carb diet in our evidence-based guide, Cholesterol and low-carb diets.

 

What lifestyle interventions can be implemented?

In the setting of dramatically elevated LDL cholesterol, consider advising your patient to do the following, in this order:13

  1. Stop drinking medium-chain triglyceride (MCT) coffee, also known as “bulletproof” coffee: If patients stop drinking fat — such as butter, coconut oil or MCT oil in coffee, or drinking other fats when not hungry — this alone can often normalize LDL cholesterol levels.
  2. Use more unsaturated fats like olive oil, fatty fish and avocados instead of saturated fat. Whether this will improve their health is unknown, but this change is likely to lower their cholesterol. 
  3. Eat only when hungry and consider adding intermittent fasting (IF) to their daily routine (IF often reduces cholesterol levels).
  4. Consider whether the patient really needs to be on a strict LCHF diet. A more moderate or liberal LCHF diet (about 50–100 grams of net carbs per day) can still achieve good results and will likely lower their cholesterol. If they decide to increase their carbs, recommend minimally processed carbohydrate foods, such as sweet potatoes, fruit, and nuts. Patients should not return to eating refined starches and sugars.

 

Should you prescribe a statin?

When LDL cholesterol is high, the question of cholesterol-lowering medication — typically statins — is often discussed. This is especially true for people with pre-existing heart disease who will likely already be on statin therapy. For those with very high cholesterol but no known heart disease, statins may slightly lower the risk of heart disease, but at the risk of potential side effects. We have to ask the clinical question if the potential benefits outweigh the potential risks in each individual circumstance.

Large population studies show a consistent, small benefit for treating those with LDL cholesterol levels above 190mg/dl. However, subset analysis for those with low triglycerides and HDL above 50mg/dl, show less of an effect or no beneficial effect. Since the number of studies and total populations in this subset are small, some feel the data is still inconclusive and we simply do not have enough evidence to claim that very high cholesterol – even in the context of other biomarkers that are optimal on a low-carb diet – is not dangerous.14

Keep in mind that statin use is not incompatible with a low-carb diet. See our guidance on history of statin use for more information.

What to do: For most patients with only somewhat elevated LDL levels, retest them in three to six months.

For patients with very high LDL, try the non-pharmacologic interventions listed above. If the response is not optimal, discuss the benefits and risks of statin therapy after a thorough assessment of cardiovascular risk.


3. Uric acid is rising

Serum uric acid levels can go up in the first few weeks of starting a low-carb diet, but they usually normalize in six to eight weeks.15 Over the long term, uric acid levels tend to decrease on low carb, along with other markers of metabolic syndrome. One study  showed uric acid going down significantly after six months on low carb.16

About 15 – 20% of the population has elevated uric acid levels, but just because some people naturally have a higher uric acid level doesn’t necessarily mean they will develop gout.17 This is especially true of those without a prior history of gout.

See our guidance on history of gout for more information.

What to do: Retest uric acid levels in two to three months if necessary. Drinking water with lime or lemon and reducing alcohol consumption may help reduce uric acid levels and minimize the risk of a gout flare.18


4. Inflammatory markers are rising

Many factors can influence the results of a C-reactive protein (CRP) or high-sensitivity-CRP (hs-CRP) test.19 Nutrition is one of these factors and studies show that low-carb and keto diets can decrease signs of inflammation, including CRP.20 However, infections and even a simple cold can increase this marker, as can food intolerances, poor sleep, or an intense workout.

Therefore the first reaction to an elevated CRP is to look for other causes, and repeat the test in three months.

If there is no alternative reason for the elevation and no improvement in inflammatory markers, you could consider the following steps:21

  1. Assess lifestyle, including non-nutrition potential causes such as inadequate sleep, poorly controlled stress, high intensity exercise, or underlying inflammatory medical condition.
  2. Eliminate processed keto products.
  3. Consider eliminating dairy. Although the highest level data suggests there is not a consistent relationship between dairy consumption and increased inflammatory markers, anecdotal reports and clinical experience suggest that some individuals may have this reaction.22
  4. Consider reducing saturated fat, especially MCT-oil coffee and processed meats.

What to do: Look for alternative causes. If none are found, try the above interventions and retest.


5. Fasting insulin is rising

Fasting insulin levels are influenced by stress, infection, steroid use and other factors, so rising levels are not always indicative of insulin resistance or pre-diabetes.23 Interpret these results in the context of other markers of insulin resistance, such as fasting glucose, postprandial glucose, and hemoglobin A1c (HbA1c). You can even consider an oral glucose tolerance test measuring both glucose and insulin levels.24

What to do: Retest in 3 months, or do a 2-hour postprandial insulin test to get a more detailed picture of the situation. Even better, consider a continuous glucose monitor (CGM) and correlate readings with an extensive food log for the most accurate information.


6. Fasting blood sugar levels are elevated

Higher blood sugars are commonly seen in the morning with patients on low-carb diets.25 This so-called “dawn phenomenon” is thought to occur from the early morning cortisol rise that increases glucose secretion from the liver. We recommend having the patient check pre- and post-prandial blood glucose levels and, if possible, consider using a CGM. If glucose levels are optimal the remainder of the day and HbA1c is not a concern, then no intervention is required.

If blood sugars remain high, ask the patient to keep a food journal and check for hidden carbs, frequent snacking, sugary drinks, and alcohol consumption. Also, query for excessive protein intake, (more than 2.0 g/kg of lean body weight) which in some susceptible individuals may provide the substrate for increased gluconeogenesis in the liver.

Time-restricted eating and intermittent fasting can help control elevated blood sugars as well. 26

In rare cases, a rising blood glucose or HbA1c, despite a low-carb diet, could be a sign of latent autoimmune diabetes in adults (LADA).27 If clinical suspicion is high, check a fasting C-peptide, GAD antibodies, and consider consultation with an endocrinologist for a definitive diagnosis. However, type 2 diabetes with lack of adherence to the low-carb diet is still a more likely explanation for hyperglycemia than LADA.

What to do: Have the patient check pre- and post-prandial glucose levels and consider keeping a food journal. Check a fasting C-peptide and GAD antibodies if LADA is suspected.


7. Liver enzymes are rising or fatty liver has not improved on abdominal ultrasound

Liver enzymes, measured by the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) tests, can go up in the first few weeks of switching to a low-carb diet; however, these enzymes can rise with weight loss in general, especially for women.28 Eventually, they almost always go down.29

Similarly, accumulating evidence shows that low-carb diets are an effective treatment for fatty liver.30 However, the benefits may not be seen immediately and may take up to a year.31 Therefore, as long as there is no progression of fatty liver, we suggest continuing to monitor at six- to twelve-month intervals.

Keep in mind that alcohol intake is still an important potential cause of elevated liver enzymes and fatty liver, and patients tend to under-report their alcohol consumption.

Emerging evidence also suggests intermittent fasting may be a powerful adjunctive treatment for fatty liver.32 Therefore adding fasting to a low-carb diet could be a particularly effective intervention.

What to do: Retest. If ALT does not go down or even increases after a few months and weight is stable, check for understanding of dietary guidance and explore other causes such as alcohol consumption or non-diet related causes. Eventual evaluation with imaging or biopsy may be needed depending on the severity and time course of the elevation. Keep in mind that sonographic improvement may take many months.


8. Blood pressure is not improving

Although a few people who adopt a low-carb diet will find their blood pressure remains elevated or even rises, most will see their blood pressure decrease.33

If elevated blood pressure does not respond or worsens on a low-carb diet, first consider non-food-related causes such as increased stress, poor sleep, sleep apnea, and other secondary causes of hypertension.34

Next, evaluate the patient’s sodium intake. While most people can safely increase their salt intake on a low-carb diet, a small subset may be salt sensitive and experience an increase in blood pressure. Continuing carbohydrate reduction but with lower sodium intake may be indicated.35

Also, consider whether the patient gets adequate potassium in the diet. This is an often-overlooked dietary variable that can have a profound effect on blood pressure. Increasing potassium-rich foods may mitigate the BP-raising effect of sodium, as well as cause additional reductions in blood pressure.36

See our evidence based guide on salt for more information.

What to do: Perform a thorough workup for secondary causes of hypertension. If none is found, experiment with reducing salt and increasing potassium in the diet, before adding medications.

 

  1. British Journal of Nutrition 2016: Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. [systematic review of randomized trials; strong evidence]

    Obesity Review 2009: Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. [strong evidence]

  2. Annals of Internal Medicine 2014: Effects of low-carbohydrate and low-fat diets: a randomized trial [moderate evidence]

    New England Journal of Medicine 2003: A randomized trial of a low-carbohydrate diet for obesity. [moderate evidence]

  3. Hyperchylomicronemia and lipoprotein lipase deficiency are also contraindications to LCHF due to the body’s inability to properly handle the products of fat digestion. This usually presents early in life, and it is rare to encounter a new diagnosis as an adult. However, if you are caring for a patient with very high triglyceride levels (above 800 mg/dL), you may want to consider specialized evaluation prior to starting a high-fat diet.

  4. [anecdotal report; very weak evidence]

  5. Nutrition Reviews 2019: Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. [systematic review of randomized trials; strong evidence]

    Cardiovascular Diabetology 2018: 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 [nonrandomized study, weak evidence]

  6. Lipids 2009: Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet [randomized trial; moderate evidence]

  7. Vascular Health and Risk Management 2009: Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention [review of observational studies, weak evidence]

    Athersclerosis Thrombosis and Vascular Biology 2015: Small Dense LDL Cholesterol Concentrations Predict Risk for Coronary Heart Disease: the Atherosclerosis Risk in Communities (ARIC) Study [observational study, weak evidence]

  8. Nutrition Reviews 2019: Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. [systematic review of randomized trials; strong evidence]

    American Journal of Epidemiology 2012: Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: A meta-analysis of randomized controlled clinical trials/strong> [systematic review of randomized trials; strong evidence]

  9. Non-HDL is the total cholesterol concentration minus the HDL cholesterol concentration. It is a useful marker as it is included on standard lipid tests and it measures all apo-B containing lipoproteins such as LDL, IDL and VLDL.

  10. Annals of Internal Medicine 2010: Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet [randomized trial; moderate evidence]

  11. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

    However, there is also evidence showing this in small population studies such as this one in athletes from Drs. Volek and Phinney.

    BMJ Open Sport and Exercise Medicine 2018: Paradox of hypercholesterolaemia in highly trained, keto-adapted athletes. [observational study, weak evidence]

  12. Clinics 2008: High ratio of triglycerides to HDL-cholesterol predicts extensive coronary disease [non-controlled study; weak evidence]

    Arteriosclerosis, Thrombosis, and Vascular Biology 1997: Relation of high TG–low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease [non-controlled study; weak evidence]

  13. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  14. Circulation 2001: Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S [Posthoc analysis of an RCT, weak evidence]

    Canadian Journal of Cardiology 1988: Cholesterol and lipids in the risk of coronary artery disease–the Framingham Heart Study. [observational study, weak evidence]

  15. Nutrition 2012: Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. [randomized trial; moderate evidence]

  16. Nutrition 2012: Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. [randomized trial; moderate evidence]

  17. Rheumatology 2009: New insights into the epidemiology of gout [overview article; ungraded]

  18. One small pilot study showed citric acid can neutralize uric acid and may reduce uric acid levels.
    Annals of Rheumatic Diseases 2015: Lemon juice reduces serum uric acid level via alkalization of urine in gouty and hyperuremic patients: a pilot study [non-controlled study; weak evidence]

    This study showed most types of alcohol, even in moderate amounts, increased risk of gout. However, it is likely that none of the participants were on a low-carb diet:
    American Journal or Medicine 2015: Alcohol quantity and type on risk of recurrent gout attacks: An internet-based case-crossover study [weak evidence]

  19. Canadian Family Physician 2017: Causes and outcomes of markedly elevated C-reactive protein levels [non-controlled study; weak evidence]

  20. Metabolism 2013: Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects [randomized trial; moderate evidence]

    Annals of Medicine 2014: Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet [randomized trial; moderate evidence]

    Diabetes Therapy 2018: Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study [nonrandomized study, weak evidence]

  21. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  22. This review of RCTs showed no association between dairy consumption and elevated CRP.

    The American Journal of Clinical Nutrition 2013: Impact of dairy products on biomarkers of inflammation: a systematic review of randomized controlled nutritional intervention studies in overweight and obese adults [systematic review of randomized trials; strong evidence]

    Therefore the evidence in support of the association is based on clinical experience of low-carb practitioners. [weak evidence] and [anecdotal reports; very weak evidence]

  23. Diabetes Care 2003: Effect of acute psychotic stress in nondiabetic subjects on β-cell function and insulin sensitivity [non-controlled study; weak evidence]

    Diabetes Care: 2006: Burden of infection and insulin resistance in healthy middle-aged men [non-controlled study; weak evidence]

    The Netherlands Journal of Medicine 2014: Steroid diabetes: from mechanism to treatment? [overview article; ungraded]

  24. This test is commonly referred to as a Kraft test after Dr. Joseph Kraft. Although it is a time consuming and cumbersome test that may suffer from lack of standardization, it may also provide unique evidence regarding the level of insulin resistance.

  25. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  26. Diabetes Research and Clinical Practice 2016: The effects of intermittent compared to continuous energy restriction on glycaemic control in type 2 diabetes; a pragmatic pilot trial. [randomized trial; moderate evidence]

    Cell Metabolism 2018: Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes [randomized trial; moderate evidence]

  27. Endocrinology and Metabolism 2018: Latent autoimmune diabetes in adults: Current status and new horizons [overview article; ungraded]

  28. American Journal of Clinical Nutrition 2008: Effect of a dietary-induced weight loss on liver enzymes in obese subjects. [non-controlled study; weak evidence]

  29. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  30. Journal of Hepatology 2019: The beneficial effects of a Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content [randomized trial; moderate evidence]

  31. This is based on clinical experience of low-carb practitioners and was unanimously agreed upon by our low-carb expert panel. You can learn more about our panel here [weak evidence].

  32. Gastroenterology Research and Practice 2017: Impact of time-restricted feeding and dawn-to-sunset fasting on circadian rhythm, obesity, metabolic syndrome, and nonalcoholic fatty liver disease [overview article; ungraded]

  33. Obesity Reviews 2009: Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities [systematic review of randomized trials; strong evidence]

  34. Journal of the American College of Cardiology 2005: The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: The emerging field of behavioral cardiology [overview article; ungraded]

    Sleep 2009: Insomnia with objective short sleep duration is associated with a high risk for hypertension [very weak evidence]

  35. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  36. American Journal or Physiology- Endocrinology and Metabolism 2017: Cardiovascular benefits associated with higher dietary K+ vs. lower dietary Na+: evidence from population and mechanistic studies [observational study, weak evidence]