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

By , , medical review by Evidence based
On a low-carb, high-fat (LCHF) or keto diet, most health markers and lab results tend to improve.
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 uses TGs as energy, replacing glucose as the body’s main fuel.

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. In these cases, a high-fat diet may worsen rather than help their triglyceride numbers.

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.

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.

Typically high-density lipoprotein (HDL) cholesterol increases, while triglycerides decrease and low-density lipoprotein (LDL) particles become larger and less dense.

All three of these changes statistically reduce the risk of future heart disease.

Generally speaking, LDL remains unchanged or the elevation of total and LDL cholesterol is so small that it is likely clinically insignificant.

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-diet and on-diet HDL, as well as the pre- and on-diet non-HDL values.

The next step is to assess the timeframe. One trial showed that a small transient rise in LDL normalized at the 1-year mark.

Therefore, if there is an early, small increase in cholesterol, it is reasonable to simply monitor 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.

In these situations, we recommend first looking at the rest of the lipid panel, keeping in mind that LDL alone may not predict cardiovascular risk as well as TC:HDL and TG:HDL ratios – especially in the absence of diabetes or metabolic syndrome.

If the rest of the lipid panel looks better – despite the elevated LDL – consider advanced lipid testing for LDL subfractions and remnant particles such as VLDL. Although we do not have evidence proving that high levels of larger, less-dense LDL aren’t dangerous, there is evidence suggesting that these LDL particles are generally less atherogenic.
In addition, multiple studies suggest remnant cholesterol may be a better risk predictor than LDL.

Next, put the LDL elevation into context by 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 elevated insulin levels. We also recommend performing a comprehensive cardiovascular risk assessment before 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 190 mg/dL (5.0 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:

  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.
  4. Consider whether the patient really needs to be on a strict low-carb 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. Your patients can explore their carbohydrate tolerance with help from our dedicated guide on carb tolerance.

You can read more about lowering LDL on a low-carb diet in our evidence-based guide.
 

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.

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.

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.

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.

4. Inflammatory markers are rising

Many factors can influence the results of a C-reactive protein (CRP) or high-sensitivity-CRP (hs-CRP) test.

Nutrition is one of these factors and studies show that low-carb and keto diets can decrease signs of inflammation, including CRP.
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 causes and repeat the test in three months.

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

  1. Perform a deeper assessment of lifestyle, including non-nutritional causes such as inadequate sleep, poorly controlled stress, high intensity exercise, or an underlying inflammatory medical condition.
  2. Eliminate processed keto products.
  3. Consider eliminating dairy. Although the highest level data suggest 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.
  4. Consider reducing saturated fat, especially MCT-oil coffee and processed meats.

What to do: Look for obvious 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.

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.

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.

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 are high throughout the day, 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.

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).

If clinical suspicion is high, check a fasting C-peptide, GAD antibodies, and consider consultation with an endocrinologist for a definitive diagnosis. However, natural progression of type 2 diabetes or lack of adherence to the low-carb diet are more likely explanations for hyperglycemia than LADA.

What to do: Have the patient check pre- and post-prandial glucose levels and consider keeping a food journal. Consider time-restricted eating/intermittent fasting, which can help control elevated blood sugars.

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.

Eventually, they almost always go down.

Similarly, accumulating evidence shows that low-carb diets are an effective treatment for fatty liver.

However, the benefits may not be seen immediately and may take up to a year.
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.

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.

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.

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.

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.

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.